Innovations in the Treatment of
Female Urinary Incontinence
James Chivian Lukban DO, FACOG, FACS
Director, Division of Urogynecology
Associate Professor of Obstetrics and Gynecology
Eastern Virginia Medical School
Norfolk, Virginia
Disclosures
• Novasys – Consultant, Speaker, Grant Recipient
• AMS – Consultant, Speaker, Grant Recipient, Facilitator
• Pfizer - Speaker
Epidemiology of Urinary Incontinence
• Prevalence
– Community – 8 to 41%
– Nursing Home – 40 to 70%
• Incidence
– 20% over a one-year period
Epidemiology (United States)
28M Women With Urinary
Incontinence
15M Women With
Stress Urinary Incontinence
Health Research International, 2005
Economic Impact
• Total Cost – 16.4 billion dollars (1994)
– Community – 11.2 billion
– Nursing Home – 5.2 billion
• Greatest cost is for care and supplies such
as laundry, pads and diapers
• Less cost for diagnosis and treatment
Definition of Urinary Incontinence
• The complaint of any involuntary leakage
of urine
Abrams P et al. Neurourol Urodyn 2002;21:167-78.
Types of Urinary Incontinence
• Transurethral
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Stress Urinary Incontinence
Urge Urinary Incontinence
Mixed Incontinence
Overflow Incontinence
Stress Urinary Incontinence
• The complaint of involuntary leakage on
effort or exertion, or sneezing or coughing
Abrams P et al. Neurourol Urodyn 2002;21:167-78.
Urge Urinary Incontinence
• The complaint of involuntary leakage
accompanied by or immediately preceded
by urgency
Abrams P et al. Neurourol Urodyn 2002;21:167-78.
Mixed Urinary Incontinence
• The complaint of involuntary leakage
associated with urgency and also with
exertion, effort, sneezing or coughing
Abrams P et al. Neurourol Urodyn 2002;21:167-78.
Overflow Incontinence
• Any involuntary loss of urine associated
with overdistention of the bladder
Abrams P et al. Scand J Urol Nephrol 1988;114(suppl):5.
Risk Factors for Female SUI
• Age and Parity
• Pelvic floor muscle denervation
and endopelvic fascial disruption
• Physical activity level
• Individual impact is variable
A QOL Problem!
Etiology of Female SUI (Anatomic)
Etiology of Female SUI (ISD)
Delancey JOL. World J Urol 2007;15:268.
Stress Incontinence Severity
Mild
Severe
Hypermobility
(Type II)
Intrinsic Sphincter
Deficiency
(Type III)
Evaluation of Urinary Incontinence
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Patient History
Voiding Diary
Physical Examination
Bedside Cystometry
Cough Stress Test
Post Void Residual Volume
Urinalysis
Patient History
• Urinary Symptoms
– Stress Incontinence
• 1) Do you leak urine when you cough, sneeze or
laugh?
• 2) Do you leak upon standing or walking?
• 3) What percentage of time do you leak with
provocation?
• 4) Do you wear a pad?
Patient History
• Urinary Symptoms
– Urge Incontinence
• 1) How many times a day do you urinate?
(frequency - > 8 voids in 24 hours)
• 2) Do you ever have a strong urge to void such that
you feel you may leak? (urgency)
• 3) Do you ever leak before reaching the toilet?
(urge incontinence)
Patient History
• Urinary Symptoms (continued)
– Urge Incontinence
• 4) How many times at night are you awakened by the need to
urinate? (nocturia - > or = to 1 time per night)
• 5) Do you ever wet the bed? (nocturnal enuresis)
• 6) Do you wear a pad?
– Overflow Incontinence
• 1) Do you feel that your stream is adequate?
• 2) Do you feel that you fully evacuate your bladder?
• 3) Do you wear a pad?
Patient History
• Medications
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Alpha-adrenergic agonists (urinary retention)
Alpha-adrenergic blockers (stress incontinence)
Anticholinergic agents (urinary retention)
Antidepressants (urinary retention)
Beta-adrenergic agonists (urinary retention)
Calcium-channel blockers (urinary retention)
Diuretics (frequency)
Patient History
• GU History
• Past Medical History
– CVA, dementia, MS, parkinsonism, SCI
• Past Surgical History
– gynecologic, anti-incontinence
• Social History
– tobacco, caffeine, occupation
Physical Examination
• Vulvae/Vagina/Urethral Meatus
(hypoestrogenemia/caruncle)
• Urethra
(hypermobility/tenderness/diverticulum)
• Pelvic Organ Prolapse
• Pelvic Exam
• Neurologic Assessment (perineal sensation,
anal sphincter tone)
Urinalysis
• Urine sampled to rule out the following:
– UTI
– hematuria
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•
•
•
rule out stones
rule out tumor
confirm by microscopic analysis
send for cytology
Bedside Cystometry
• Requires transurethral catheter attached to a
50 cc syringe
• Aliquots of 50 cc of sterile water are
introduced
• Normal desire and maximum cystometric
capacity are determined
• Meniscus is observed for rises in level
during filling
Post Void Residual Volume
• Measurement of residual volume of urine in
bladder immediately after voiding
• Determined through transurethral catheter
placement or ultrasound
• A volume of > 75 cc may be associated with
voiding dysfunction and predispose one to
overflow incontinence and UTI’s
Cough Stress Test
• Performed at maximum cystometric
capacity
• Observation of leakage with a strong cough
• High sensitivity in detecting stress
incontinence
Multichannel Urodynamics
• Mixed incontinence
• Recurrent
incontinence
• Voiding dysfunction
Treatment of Stress Incontinence
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Timed voiding
Kegel contractions
Biofeedback
Functional electrical stimulation
Medical treatment
Anti-incontinence surgery
Bulking agents
Timed Voiding
• Regular bladder evacuation independent of
urge to maintain an empty bladder
Kegel Contractions
• Exercises of the pelvic floor musculature
• 15 deliberate, quick, hard contractions of 10
second duration with 15 second intervals of
muscle relaxation
• 3 times a day for a total of 45 contractions
Biofeedback
• Vaginal cones
• Vaginal manometry or
electromyography
• Concomitant measurement of abdominal
muscle activity
• 1-2 times a week for 6 weeks
Functional Electrical Stimulation
• Introduced by Caldwell in 1963
• Utility in treating musculature in patients
unable to isolate the pelvic floor
• Often used in conjunction with biofeedback
• Symptom improvement in approximately
60% of patients
Payne CK. Electrostimulation. In: Urinary Incontinence, O’Donnell
PD, ed. 1997, 287-94.
Overall Effectiveness of Conservative Therapy
• Latthe PM et al. Nonsurgical Treatment of
SUI: Grading of Evidence in Systematic
Reviews. BJOG 2008;115:435-444.
• Meta-analysis of 6 reviews
• PFMT better than placebo
• Strong recommendation based on intermediate
quality evidence
• Questionable durability of effect
Medical Therapy for SUI
• Duloxetine Hydrochloride
• Inhibits reuptake of serotonin and
norepinephrine
• Enhances urethral function in animal models
through Onuf’s nucleus
• Reduction in IEF in 51% (drug) vs. 31%
(placebo) at 6 weeks
• Not currently available in US for SUI
Cardozo L et al. Curr Med Res Opin 2010;26:253-61.
Anti-incontinence Surgery
• Anterior colporrhaphy with Kelly plication
• Retropubic urethropexy
– Burch
– Marsahll-Marchetti-Krantz (MMK)
• Suburethral sling procedure
– Traditional
– Mid-urethral Tape
TVT
Nillson CG et al. In J Pelvic Floor
Dysfunct 2009;6:72-3.
Monarc Needle Design
• Helical Needles
Transobturator Landmarks
Adductor longus
Urethra
Obturator canal
SAFE ENTRY ZONE
of MONARC
NEEDLE
Monarc Needle Passage
Monarc Mesh Position
SPARC/TVT
Monarc & Normal Anatomic
Urethral Support
Barber MD et al. Obstet Gynecol
2008;111:611-21.
Monarc Data
• Barber et al. Obstet Gynecol 2008;111:611
• Monarc non-inferior to TVT in RCT of 170
patients with SUI at a mean follow-up of 18
months
• TVT exhibited higher incidence of bladder
perforation (7% vs. 0%) and more postoperative
voiding dysfunction.
Mini Arc
Mini Arc
MiniArc Data
• Kennelly M et al. J Urol (In Press)
• Multi-center study with 188 patients and 12
month follow-up
• Mean operative time – 11 minutes
• Mean EBL – 41.7 cc
• Mean length of stay – 9.5 hours
• Mean pain score (0-10) at discharge – 1.3
MiniArc Data
• Cough-stress Test negative in 90.6 %
• One-hour PWT < 1 g in 84.5 %
• Adverse events included UTI (4.3%),
temporary retention (3.2%), dyspareunia
(2.1%) and vaginal extrusion (2.1%)
Bulking Agents
• For the treatment of low-threshold stress
incontinence
• Collagen (bovine) and Durasphere (carbon-coated
beads) typically employed in past
• Coaptite (Calcium hydroxyl petite)
• Introduced via intra-urethral or peril-urethral
injection
• Improvement seen in approximately 70% of
patients
Mayer MD et al. Urology
2007;69:876-80.
Renessa
• Office treatment
• Radiofrequency treatment of the bladder
neck and proximal urethra
• Less effective than operative intervention
• May be alternative to physical therapy
Elser DM et al. J Min Invasive
Gynecol 2009;16:56-62.
SUI Therapeutic Spectrum
Invasiveness is broadly defined to include approach (surgical vs non-surgical),
anesthetic requirements, risk to the patient, post-treatment pain and discomfort,
recovery burden, and need for multiple or chronic treatments.
The Novasys Medical Renessa System
• Single treatment in office
• 20-30 minute total procedure time
• Performed using local anesthesia with or
without oral anxiolytic
• Palpation-based (no cystoscopy)
• Excellent safety profile, well tolerated
• No incisions, bandages, or dressings
• Rapid recovery with minimal limitations
Treatment with Renessa
• Transurethral Renessa probe
with balloon and 4 needle
electrodes
• Each 60-second treatment cycle
heats 4 submucosal sites to 65ºC
• 9 treatment cycles denature
collagen at 36 sites within the
bladder neck and proximal
urethral submucosa
• Automatic safety features
monitor tissue temperatures and
impedance
Renessa Mechanism of Action
• Reduces bladder neck and
proximal urethral compliance
• Limits inappropriate bladder
neck and proximal urethral
opening during increases in
intra-abdominal pressure
• Improves continence without
affecting normal urination
Abdominal Pressure
SUI Hypermobility and Funneling
• Incontinence occurs when bladder outlet hypermobility
is accompanied by inappropriate opening (“funneling”)
of the bladder neck and proximal urethra1
• “The cure of stress incontinence does not require the
correction of proximal urethral hypermobility”2; it
requires the prevention of bladder neck and proximal
urethral funneling
1. Blaivas JG, Heritz DM. In: Blaivas JG, ed. Evaluation and Treatment of Urinary Incontinence. New York:
Igaku-Shoin; 1996:22-45.
2. Klutke JJ, Carlin BI, Klutke CG. Urology. 2000;55:512-514.
RF Collagen Denaturation and SUI
Collagen triple helix molecule
1. Low-temperature RF delivery results in thermal collagen denaturation
— Elongated, crystalline collagen becomes random-coil gel
2. Collagen denaturation/healing phase occurs
— Results in reduced compliance of denatured tissue sites
3. Collagen denaturation is performed circumferentially within the bladder
neck and proximal urethral submucosa
— Reduces regional (bladder neck and proximal urethral) compliance
4. Results in reduction or inhibition of inappropriate bladder neck and
proximal urethral luminal opening during bladder descent
Histology Post Renessa
• Subnecrotic submucosal
target temperature results in
localized collagen
denaturation
• No effect on overlying mucosa
or deeper urethral wall tissues
• Healed submucosal sites
measure only ~200 µ
in diameter
• No luminal narrowing or
stricture formation occurs
2 Months
(porcine)
Prospective Long-Term Durability Trial
• A multicenter, prospective, 36-month, open-label, single-arm clinical
trial
• Enrollment completed (137 women; 13 sites), December 2006
• 12-month follow-up completed in January 2008
• Primary effectiveness end point:
– The percent of treated subjects that achieve a 50% reduction in the
number of daily incontinence episodes at 12 months vs baseline
• Secondary effectiveness end points
– Increase in overall I-QOL score from baseline to 12 months from the IQOL questionnaire
– ≥50% decrease in 1-hour in-office pad weight from baseline to 12 months
– Improvement in the UDI-6
– Patient satisfaction/impression of improvement
Elser DM, Mitchell GK, Miklos JR, et al. J Minim Invasive Gynecol. 2009;16:56-62.
24-Month Results
• 75.6% of women had ≥50% reduction in leaked volume on
1-hour in-office pad weight test
– 41% were dry (28% no leaks; 13%,<1 g leakage)
• A ≥50% leak reduction from baseline in leaks due to
activity was reported in:
– 55% of patients evaluated at 24 months (P=.0001)
• Significant improvements were seen in median I-QOL
scores
– 66% experienced ≥10-point improvement over baseline
Data on file. Novasys Medical.
24-Month Results
• Mean overall UDI-6 scores also improved significantly
(P<.0001)
– 60.3% experienced some degree of improvement
• Overall, 60.3% of patients were satisfied
• 52% would recommend the procedure to a friend
• No serious adverse events occurred at any time
posttreatment
Data on file. Novasys Medical.
Safety of Renessa
• No serious adverse events have been reported in any clinical trial
• The majority of adverse events are mild and typically resolve within a few
weeks posttreatment. Adverse events include:
– Dysuria 5%-9%
– Hematuria 1%
– Urinary tract Infection 3%-4%
– Retention 1%-4%
– Worsening incontinence due to overflow incontinence, overactive
bladder, or intrinsic sphincter deficiency
• Rates of all “worsening incontinence” seen in clinical trials, including
transient urgency or urge incontinence = ~15%
• Reported “worsening incontinence” in the commercial setting = ~3%
Treatment Site Confirmation
Post Treatment Appearance
Periurethral Vasculature Pre Treatment
Periurethral Vasculature Post Treatment
Treatment Algorithm for Stress Urinary Incontinence
SUI (objective findings)
Timed Voiding/Kegel Exercises
Biofeedback/Functional Electrical Stimulation
Surgical Therapy/Bulking Agents